Continuing Education Activity

Aniseikonia occurs when there is a difference in perceived image size or shape. It is usually caused by anisometropia, called optical aniseikonia, or by changes in the macula, such as edema or distortion, called retinal aniseikonia. Aniseikonia at a young age can result in amblyopia. Aniseikonia at a later age can cause asthenopia, headache, diplopia, dizziness, nervousness, imbalance, nausea, spectacle intolerance, ocular suppression, and distorted space perception. Aniseikonia is best measured with an eikonometer, but these are usually unavailable. It can also be calculated in the clinic by dissociating the two images of the eyes and estimating the difference in shape and size. This activity highlights the role of the interprofessional team in evaluating and managing patients with aniseikonia.

Objectives:

• Describe the difference between aniseikonia and anisometropia.
• Review the various causes of aniseikonia.
• Summarize tests used to evaluate for aniseikonia.
• Explain the treatments used in managing aniseikonia.

Introduction

The word aniseikonia derives from the Greek words "an," "is," and "eikon," which mean "not," "equal," and "image," respectively. Aniseikonia occurs when there is a difference in an image's perceived size or shape and is often caused by anisometropia, which is a difference in refractive error. When aniseikonia is caused by anisometropia, it is called optical aniseikonia. Aniseikonia can also be caused by changes in the shape and location of the macula and is then called retinal aniseikonia.[1][2] 

Aniseikonia at a young age can result in amblyopia.[3] Aniseikonia at a later age can cause asthenopia, headache, diplopia, dizziness, nervousness, imbalance, nausea, spectacle intolerance, ocular suppression, and distorted space perception.[1] It is thought that over 0.75% of aniseikonia can start to cause symptoms, that at 1 to 3% definite symptoms are present, and that more than 5% of aniseikonia is incompatible with binocular vision.

In many cases, optical aniseikonia is predicted by calculating the difference in spectacle magnification of the right and left spectacle lens. In clinical practice, the rule of thumb that every 0.25 diopter of anisometropia causes about 0.25% to 0.5% of aniseikonia is often used. However, studies have shown that these rules of thumb significantly overestimate aniseikonia and direct measurements are much more accurate.[4] 

Aniseikonia can be subdivided into symmetrical and asymmetrical aniseikonia. Symmetrical aniseikonia further subdivides into spherical (overall difference in magnification) and cylindrical (a difference in magnification in one orientation). Asymmetrical aniseikonia is also called distortion and occurs when perceived image size differences are unequal in different parts of the visual field.

In the case of prismatic distortion, the difference in image size increases in one direction. In the case of pincushion distortion, the corners of one image are stretched more outward than the other. In the case of barrel distortion, the corners of the image appear squeezed inward. In the case of oblique distortion, one image is rotated relative to the other. Aniseikonia is most accurately measured with an eikonometer, but most clinics do not have one. Many other techniques of measuring aniseikonia exist, some of which require minimal equipment and can be done in a regular eye clinic.[5] All these tests employ different methods to dissociate the two ocular images and have developed a method to compare the shape and size difference of the images perceived by the two eyes.

Aniseikonia only occurs when the eyes are being used together and does not occur if vision is suppressed or reduced, as may be the case in alternating strabismus and unilateral amblyopia or ocular disease.[3] Anisometropia also does not cause aniseikonia in specific situations described by Knapp's law. According to Knapp's law, axial anisometropia does not cause aniseikonia when the refractive difference between the eyes is solely due to a difference in the axial length (distance from the cornea to the retina) and when the correcting lens is placed at the anterior focal point of the eye which is about 16 mm in front of the cornea. However, clinical applications of Knapp's law are limited as anisometropia is usually not purely axial. The retina is usually stretched in the eye with the increased axial length (a cause of retinal aniseikonia), and placing a correcting lens at 17 mm in front of the eye is impractical.[6]

Aniseikonia is treated with the surgical or medical correction of the underlying cause, optically with refractive surgery, clear lens exchange, secondary intraocular lens (IOL) placement, contact lenses, or via spectacle correction with iseikonic lenses.[1] When this is not possible, occlusion of one eye may be the only alternative.

Etiology

Optical Aniseikonia. This is caused by a difference in refractive error. A disparity in the eye's spherical refractive error is called anisometropia, while aniso-astigmatism is reserved for dissimilarity in the amount or the orientation of cylindrical error. Anisometropia causes a difference in size, while aniso-astigmatism causes a difference in the shape of an image.

When the vertical astigmatic meridian has comparatively less plus (or more minus) dioptrical power, objects appear vertically compressed or horizontally elongated in the affected eye. Objects appear vertically stretched and horizontally compressed when the horizontal meridian has less plus dioptrical power.

Besides a difference in the dioptrical power of the spectacle lenses, other parameters such as index of refraction, lens thickness, vertex distance, and base curve affect spectacle magnification and can result in optical aniseikonia. Changes in the cornea and the crystalline lens can cause anisometropia and as well as aniso-astigmatism, while changes in the length of the eyeball (axial length) or a difference in the refractive index of the vitreous cavity contents can only cause anisometropia and do not result in aniso-astigmatism.

Spectacle lenses may cause a change in the shape of objects as well. High minus lenses will cause a barrel type of distortion (the corners of the image appear squeezed inward), and high plus lenses will cause a pincushion type of distortion (the corners of the image appear stretched outward). Unequal barrel or pincushion distortion between the two eyes can also result in optical aniseikonia. Other types of distortion that cause aniseikonia include 

Causes of Optical Aniseikonia

Caused by the Cornea

• Keratoconus is caused by thinning of a portion of the cornea and often affects one eye more than the other. It causes asymmetrical progressive myopia and high amounts of astigmatism.[7] This condition can be inherited and is associated with eye rubbing, allergies, atopic disease, and some collagen vascular diseases.[8]
• Corneal edema can be caused by contact lens overwear, some medications such as amantadine (for Parkinson disease), netarsudil (for glaucoma), and belamtamab mafodotin (for multiple myeloma), and corneal endothelial diseases such as Fuch dystrophy and complications from cataract surgery. 
• Many types of corneal stromal and surface diseases are categorized into those caused by injury, inflammation, infection, and dystrophy. 
• Corneal surgeries that may leave the patient with anisometropia are intentional (monovision correction) or unintended unequal LASIK, PRK, and radial keratotomy refractive correction. Radial keratotomy often results in progressive hyperopic changes that are often unequal and may eventually result in anisometropia. Other surgeries that can cause optical aniseikonia are corneal epithelial scraping, corneal crosslinking, radial keratotomy, phototherapeutic keratotomy, and INTACS.

Caused by the Crystalline Lens

• Cataracts generally cause an increase in the refractive index of the crystalline lens resulting in more myopia.
• Unilateral crystalline lens removal resulting in aphakia was historically one of the most common causes of clinically significant aniseikonia. Advances in cataract surgery and intra-ocular lens implantation have made this condition less common.[9]
• Hyperglycemia has been reported to cause refractive changes of all types, even though in clinical practice, high blood sugar levels are generally associated with increased myopia.
• An accommodative spasm can occur due to medications such as pilocarpine or excessive time spent focusing.
• Multiple other medications besides pilocarpine are associated with refractive changes. These include topiramate, acetazolamide, sulfamethoxazole/trimethoprim, indapamide, promethazine, spironolactone, isosorbide dinitrate, bromocriptine, tetracycline, corticosteroids, hydrochlorothiazide, penicillamine, quinine, metronidazole, isotretinoin, and aspirin. While the mechanism of action is not always known, for some medications such as topiramate, the refractive change is caused by an anterior movement of the lens and not a change of accommodation or refractive index. 
• Lens subluxation will usually cause an increase in astigmatism as the subluxation process progresses and after complete dislocation results in a larger hyperopic shift. This can be caused by simple ectopia lentis, in ocular diseases such as pseudoexfoliation syndrome and aniridia, and systemic diseases such as Marfan syndrome, Homocystinuria, and Ehlers-Danlos syndrome.
• Unilateral cataract surgery. While cataracts are usually bilateral, they may develop at an unequal rate, and surgical intervention may be chronologically spaced apart. In most studies, the second eye undergoes cataract surgery immediately after the post-operative period has ended for the first surgery for only 30 to 40 percent of patients.[10][11] Many patients with a high refractive error before surgery may be left with anisometropia until surgery is performed on the second eye. If these patients desire spectacle correction, then optical aniseikonia may occur. Another procedure that affects the refractive power of the eye at the plane of the lens is the Implantable Collamer Lens (ICL). While the ICL is often used to correct high myopia, if it is done in one eye, or the power was calculated such that anisometropia was the result, spectacle correction could cause aniseikonia.[12]

Caused by the Vitreous Space

• Silicone oil is used for retinal tamponade and may cause hyperopic or myopic shifts based on posture and phakic, pseudophakic, or aphakic status of the eye.[13]
• Intravitreal gas such as sulfur hexafluoride or perfluoropropane is used for retinal tamponade and may generate a large myopic shift of up to 50 diopters.[14]

Caused by a Difference in Axial Length

• Anisometropia and the resultant aniseikonia, when due to an increase in axial length, can be congenital and, when not treated, can lead to amblyopia. Congenital anisometropia is predominantly caused by genetic predisposition but can also be caused by congenital glaucoma.[15][16]
• When anisometropia is developmental, it is mainly caused by genetic predisposition. 
• Strabismus can also be a trigger for the development of anisometropia.[17]
• Iatrogenically induced changes in axial length occur in scleral buckle procedures. In one study, an average of 0.99 mm increase in axial length caused myopia to increase by 2.75 diopters.[18][19] Aniseikonia is a common problem and occurs in a significant percentage of patients after scleral buckle procedures.[19]

Retinal Aniseikonia. This is caused by a distortion of the macula.[2]

Causes of Retinal Aniseikonia

• Macula swelling causes a pincushion type of distortion as well as micropsia.[20][21][22] Causes of swelling are generally macula edema, which can be caused by central serous retinopathy, diabetic and cystoid macula edema, wet age-related macula degeneration, retinal vein occlusion, and others. Since macula edema causes a change in the distance from the cornea to the retina (axial length), it can be a cause of anisometropia resulting in optical aniseikonia as well. For every 1000 microns of elevation, about 3 diopters of increased hyperopia are expected to occur. 
• Shrinking of the macula will cause a barrel type of distortion and macropsia.[22] The most common cause of involution is macula staphyloma. As with edema, for every 1000 microns of increased axial length, an increase of 3 Diopters of myopia is expected. 
• Macula distortion can be caused by retinal dragging, scarring, inflammation, and infection. Common causes are epiretinal membrane, macula hole, vitreomacular traction syndrome, proliferative retinopathy (diabetic and other types), vitreoretinal inflammation and strands, retinal granuloma, retinopathy of prematurity, and others.[2][23]

Altered Brain Function. This can be the cause of symptoms of micropsia and macropsia seen in conditions such as Alice in Wonderland syndrome, Charles Bonnet syndrome, migraine, and hypnagogic/hypnopompic hallucinations.[24][25] 

While these conditions may present with complaints that resemble those of aniseikonia, they can be ruled out as they generally affect both eyes. In theory, conditions that alter the visual pathways behind the retina can create aniseikonia as well. However, there are no cases reported in the literature. Neural adaptation to the reversal of optical aniseikonia, even when it has been longstanding, has been well studied.[26]

Epidemiology

Aniseikonia has not been measured in the general population. One hospital-based survey for aniseikonia of patients with binocular vision complaints showed that 7.8% had measurable aniseikonia, and 4% had disruption of fusion and stereopsis. This same report surveyed orthoptists in the USA and recorded that the majority evaluate aniseikonia and that their treatment was limited to the fitting of contact lenses and occlusion or fogging of one of the eyes.[27] 

Aniseikonia has been studied in specific populations, such as in patients after undergoing a scleral buckle procedure. One report showed that 6% of patients experienced aniseikonia after a scleral buckle procedure, and only 1% had persistent aniseikonia that could not be treated.[19]

Aniseikonia is also more common after unilateral cataract surgery. Second-eye cataract surgery is done in about 70% of cases leaving 30% at risk for aniseikonia.[28] One study found that 40% of all patients with unilateral or bilateral pseudophakia had clinical findings of aniseikonia.[29] Researchers developed different formulas to estimate the risk of aniseikonia after cataract surgery.[30][31]

Anisometropia is one of the most common conditions leading to aniseikonia and, by definition, occurs when there is more than 1 diopter difference in the refractive error. In one study, the prevalence of anisometropia was 1.96% at six months, 1.27% at five years, and 5.77% for those 12 to 15 years.[32] 

Aniso-astigmatism is present when the amount of astigmatism is over 1 diopter. While less well studied, aniso-astigmatism also occurs when there is more than one diopter of difference in one of the meridians. This can occur when there are relatively low amounts of astigmatism in each eye, but one eye has "with the rule" and the other eye "against the rule" astigmatism. In one study, the amount of aniso-astigmatism was 7.7% in 6 to 7-year-olds and 5.6% in 12 to 13-year-olds.[33]

The Sydney Myopia Study reported that in 6-year-olds, anisometropia and aniso-astigmatism were more common in myopes and associated with amblyopia, exotropia, low birth weight, and older maternal age. The same study revealed that anisometropia was associated with increased axial length and aniso-astigmatism with higher corneal astigmatism.[34] These studies do not reveal a racial or sex predilection. 

Researchers found that 31% of patients with congenital glaucoma also had anisometropia of 2 diopters or more.[35] Keratoconus was also strongly associated with anisometropia, with one study citing a 5.5-fold increased risk of 1 diopter or more of anisometropia in patients with keratoconus.[36]

History and Physical

A thorough history that includes questions about asthenopia, headache, diplopia, dizziness, nervousness, imbalance, nausea, spectacle intolerance, distorted space perception, as well as previous ocular surgery and ocular disease, can alert the clinician to the presence of aniseikonia. Lensometry of the habitual spectacles, as well as a full refractive evaluation that includes both objective and subjective refractive data, can determine the presence of anisometropia.

Binocular testing, including tests of extra-ocular motility, ocular alignment, and stereopsis, can detect strabismus, ocular suppression, and amblyopia. Finally, a dilated fundus exam can rule out causes of optical aniseikonia, such as keratoconus and cataracts, as well as retinal aniseikonias, such as macula edema and epiretinal membrane.

Evaluation

Testing for Retinal Aniseikonia  

• Amsler Grid. This test helps to detect barrel and pincushion distortion and evidence of dragging or other types of distortion of the macula. This test measures distortion in the central 20 degrees of the macula. There are several types of Amsler grid tests. The most common consists of a square grid of black lines on a white background with a black dot in the center. Variations on this grid are white lines on a black background, 1 degree versus 1/2 a degree per square in the grid, and the presence of diagonal lines from the corner of the grid toward the center. Some grids only have horizontal lines or just dots.[37]
• Other testing methods for metamorphopsia include an experimental 3D digital device, the M-chart (Inami Co., Tokyo, Japan), which allows quantification of the amount of metamorphopsia, and the Preferential Hyperacuity Perimeter that tests the central 14 degrees of the macula.[38][39][40]
• Direct assessment of the retina through a dilated fundus exam is often supplemented with ancillary tests such as optical coherence tomography of the macula. It is central to the diagnosis and correct treatment of underlying retinal pathology.

Testing for Optical Aniseikonia

• In practice, the most common method to estimate aniseikonia is by calculating the difference in spectacle magnification between the two eyes. The formula for spectacle magnification (SM) for a thin lens is SM = 1/(1-dFsp). d is the distance in meters from the spectacle lens to the entrance pupil.
• The distance from the spectacle lens to the apex of the cornea (called vertex distance) can be measured with a distometer. This distance is generally close to 12 mm (0.012 m).
• The distance from the apex of the cornea to the entrance pupil is assumed to be an additional 3 mm (0.003 m). Therefore, d is usually close to 15 mm (0.015 m). 
• Fsp is the power of the lens in diopters.  
• If we apply this formula for a plus 1 diopter lens positioned at a vertex distance of 12 mm, the formula allows us to calculate a 1.5% magnification. In contrast, a minus 1 diopter lens positioned at the same distance will create 1.5% minification.[31]
• Clinicians often employ a rule of thumb that 1 diopter of anisometropia generates about a 1 to 2% difference in image size.[41]
• Online calculators are available to clinicians to make these calculations quickly and easily.
• Corneal topography or, when unavailable, manual keratometry can be used to test for corneal steepening or flattening as the cause of anisometropia.[42]

Optical and Retinal Aniseikonia Tests

• A relatively simple test compares the size of diplopic images. In this test, the patient is made to see double with a horizontal or vertical dissociating prism. The width or height of the image can then be compared. Different size lenses are then held in front of one of the eyes until the perceived size of the two images is equal. A size lens creates a certain percent magnification. Size lenses are not commercially available but can be manufactured. Different percentages of magnification of size lenses are achieved by creating a lens that acts as a small afocal telescope. The telescope will magnify in one orientation and minify when it is flipped over.
• Size comparison of images observed by each eye can also be made during the alternating cover test. Instead of creating diplopia with a prism, the perceived size is compared during the alternating cover test. Size-lenses are then used to magnify the smaller appearing image to be equal in size to the image that initially appeared larger.[5][43]
• The Turville test evaluates aniseikonia in the vertical meridian. Using a device developed by Morgan, in which the two eyes are dissociated, each eye sees two horizontal lines separated by a vertical line. An unequal distance between the horizontal lines on each side indicates aniseikonia. Size-lenses can, again, be used to make the lines an equal distance apart in each eye.[44]
• Testing for aniseikonia can be done with a Maddox rod and two light sources. This test also called the Brecher test, employs a Maddox rod placed over one eye to dissociate the two eyes. Dissociation can be done with a Maddox rod placed over each eye as well. This is called the Miles test. The two lights are separated horizontally or vertically to measure horizontal or vertical aniseikonia, respectively. Size lenses can then be used to eliminate a difference in the separation of the lights.[45]
• The Robertson Technique employs a Maddox rod placed over one eye and a light source that is moved away so that the observer's visual axis does not pass through the optical center of the spectacle lenses. When anisometropia causes optical aniseikonia, Prentice's rule predicts a larger displacement of the image falling through the higher plus lens. This displacement can then be neutralized with a prism. The amount of prism required to neutralize the image displacement is then converted to an aniseikonia percentage. Since the observed image is moved away from the optical center, this test evaluates dynamic aniseikonia and not static aniseikonia, as is the case when a non-moving image is evaluated by the observer.[46][47][46]
• The (Awaya) New Aniseikonia Test (Good-Lite Company, Tokyo, Japan) uses red-green glasses to dissociate the two eyes and a booklet with red and green half-circles of different relative sizes. The observer finds the image where the half circles appear to be the same size. If, in reality, the half-circles are a different size, a diagnosis of aniseikonia is made. The amount of aniseikonia can be determined from this test as well.[48]
• An auto-stereoscopic smartphone was programmed to display half moon images similar to those in the New Aniseikonia Test. The auto-stereoscopic effect allows dissociation of the two eyes. In the test, the size of the two half-moon images is compared until they are deemed equal in size. The percentage of the actual size difference between the two half-moon images is the amount of aniseikonia present.[49]
• The Aniseikonia Inspector version 3 (Optical Diagnostics, Culemborg, The Netherlands) employs red-green glasses to dissociate the eyes and displays a red and green line on a computer screen. The lines can be oriented vertically, horizontally, and diagonally and the program allows the observer to match the apparent length of the two lines. The adjustment of the lines is done twice, with at the start of the test, one line displayed as 25% smaller and the second time as 25% larger. The average result of the two tests is used to determine the level of aniseikonia. One advantage of this test is the large range of aniseikonia it allows to be tested.[50]
• The space eikonometer is a very accurate test and is considered the gold standard for measuring aniseikonia. It requires single binocular vision with visual acuity of 20/60 or better and the ability to perform a relatively complex task of aligning four images of lines to be at an equal distance around a central target. The device was developed and sold by American Optical in 1951 and is no longer in production. This device can measure up to 5% of aniseikonia. It was developed by Adelbert Ames in the 1940s and, for this reason, is also called the Ames eikonometer.[51][5]
• The Contrast-balanced Aniseikonia Test is useful for patients with anisometropic aniseikonia that have suppression and amblyopia as well. The intensity or brightness of the image presented to the amblyopic or suppressed eye can be increased to allow for a better comparison of the perceived size of the two images.[46]

Treatment / Management

Treatment for Retinal Aniseikonia

Medical Treatment. This generally emphasizes treatment of the underlying chorioretinal disorder.

• The most common treatment of aniseikonia, contact lenses, do not treat retinal aniseikonia. Contact lenses can create similar size images on the macula, but if the retina is swollen (as is the case with edema) or stretched (as is the case with high axial myopia), the photoreceptors will be spread out over a larger area, and the image will be registered as being smaller.
• Optical solutions that form different size images on the retina, such as iseikonic lenses or specially designed combinations of contact and spectacle lenses, are hard to come by, expensive, and technically demanding to create.
• Retinal aniseikonia generally presents with a significant amount of asymmetrical (prismatic, pincushion, barrel, oblique) aniseikonia, which can not be treated optically (i.e., with iseikonic lenses or contact lenses). 
• Most causes of retinal aniseikonias, such as central serous chorioretinopathy, macula edema, and epiretinal membrane, are unstable. This makes the implementation of an optical treatment plan impractical.

Optical Treatments for Retinal Aniseikonia

• Contact lens-spectacle lens combinations. A high minus contact lens can be combined with a high plus spectacle lens to create spectacle magnification that can offset retinal micropsia. This is also called a Galilean-telescopic solution. The opposite holds as well (high plus contact lens/high minus spectacle lens/offset retinal macropsia).
• Iseikonic spectacle lenses, when available, can be a good solution as the size of the image projected on the retina can be changed to adjust for retinal swelling or stretching. 

Treatment of Optical Aniseikonia. This, on the other hand, has many solutions.

• Reduction of vertex distance. The shorter the vertex distance, the less the spectacle magnification, and while it can not eliminate it, this simple step often reduces the amount of aniseikonia to acceptable levels. 
• Contact lens(es). Contact lenses are positioned very close to the entrance pupil of the eye, and even highly divergent lens powers will generate minor amounts of aniseikonia. Therefore, using contact lenses on one or both eyes to fully correct the patient's refractive error is a highly effective way of reducing optical aniseikonia to tolerable levels.
• Contact lens-spectacle lens combinations. Often it is most desirable to the patient to eliminate anisometropia with a contact lens that corrects only the difference between the anisometropic spectacle lenses. Spectacle lenses often provide superior correction for presbyopia and astigmatism, are generally more effective in filtering out different light wavelengths (sunglasses, blue-light blocking lenses), and spectacles provide protection as well. In these cases, only one eye is fit with a contact lens, reducing the cost and risk of contact lens-related infection and inflammation. A special pair of isometropic glasses are then prescribed to be worn in combination with the contact lens.
• Undercorrection of one spectacle lens. When neither surgical intervention, contact lenses, nor iseikonic spectacles are an option, anisometropia may be reduced by under or over-correcting one of the spectacle lenses. While this may cause one eye to see blurry, this may allow for better depth perception.
• Neuroadaptation. There is evidence that rapid neuroadaptation can occur to adjust for the onset and after surgical reversal of aniseikonia.[12][26] Therefore, in some cases, when other solutions are unavailable, prescribing an anisometropic spectacle, Rx may allow neuroadaptation and some degree of binocularity.
• Refractive surgery (e.g., LASIK, PRK, RK) is a common way to correct optical aniseikonia.[52][53]
• Clear lens exchange, also called refractive lens exchange, is when the crystalline lens is surgically removed and replaced with an intraocular lens implant. This procedure is used less often as a solution for aniseikonia, but with the advent of good multifocal intraocular lenses, many surgeons and patients alike feel the benefit outweighs the relatively small risk of complications such as infection and retinal detachment.[53]
• Phakic intraocular lens placement is a procedure where a lens is placed inside the eye without removing the crystalline lens. While some studies reported adequate safety and good results, the potential risk of corneal decompensation as well as retinal detachment, and elevated intraocular pressure are all reasons why this is a less common treatment for aniseikonia as well.[54][55]
• Secondary IOL placement is the placement of an intraocular lens in an aphakic eye or to replace a deficient lens. Advances in intraocular lens technology, specifically light-adjustable lenses, have allowed for a very precise isometropic refractive endpoint.[56]
• Iseikonic spectacle lenses work by altering the vertex distance, base curve, center thickness, and index of refraction of the spectacle lens material to provide magnification of one lens compared to the other. The formula for total magnification produced by iseikonic lenses (Mt) equals the magnification due to lens shape factor (Ms), which depends on the index of refraction (n), base curve (D1) and thickness (t), and the lens power factor (Mp), which depends on the dioptrical power of the lens (Dv) and the vertex distance in meter (h).
  • Mt = Ms x Mp
  • Ms = 1/(1-(tD1/n)) 
  • Mp = 1/(1-hDv)
• The impact in magnification by alteration of lens variables is as follows:
  • Increasing vertex distance (h): increases magnification for plus and minification for minus lenses.
  • Steepening the (front) base curve (D1): increases magnification and decreases minification for lenses of all powers.
  • Increase lens thickness (t): increases magnification and decreases minification for lenses of all powers.
  • Increase lens power (Dv): increases magnification for plus and minification for minus lenses.
  • Increase index of refraction (n): decreases magnification and increases minification.
• Since, in optical aniseikonia, due to anisometropia, the lens power (Dv) is fixed, four other variables affect the design of iseikonic lenses: base curve, center thickness, index of refraction, and vertex distance.[57]
• If the difference between the eyes is up to 3 diopters, iseikonic lenses are usually an effective solution. At the maximum correction of 3 diopters, the iseikonic lens would look very different due to a large difference in center thickness and base curve. 

Occlusion of one eye is a solution of last resort but may be used to avoid dangerous situations such as driving with diplopia or while waiting for the implementation of other solutions to be implemented. 

Advantages of Contact Lenses for Aniseikonia

• It is the most effective and convenient way of eliminating optical aniseikonia.
• It can be combined with a spectacle lens to create a magnifier to treat retinal aniseikonia.
• Contact lenses can usually immediately be dispensed from trial lens inventory at the initial visit, and the lens power can be changed easily and quickly in the case of changes of refractive error or aniseikonia, making it a convenient solution for unstable conditions and those that require immediate intervention.

Disadvantages of Contact Lenses for Aniseikonia

• Many patients may not be able to wear contact lenses due to allergies, dry eye, or problems handling the lenses. 
• Contact lenses alone can not treat retinal aniseikonia.

Advantages of Iseikonic Lenses

• It can treat both optical and retinal aniseikonia.
• It can be the only option when surgical intervention or contact lenses are not possible.

Disadvantages of Iseikonic Lenses

• It is hard to find a local provider of lenses. The advent of optical vendors of iseikonic lenses on the internet that will assist with the design of the lenses provides hope that this solution will be used more often. 
• One lens is usually heavier than the other, creating an unequal distribution of weight.
• One lens is generally thicker than the other. This is cosmetically unattractive and can make frame selection hard.
• The iseikonic lens induces prism and distortion.
• One eye will look larger than the other affecting acceptable cosmesis for the patient.

Differential Diagnosis

Anisometropia causes induced prism. When anisometropia is accompanied by symptoms of asthenopia, diplopia, nausea, imbalance, and headache, the assumption is generally made that aniseikonia is the cause. However, anisometropic spectacles can cause similar symptoms due to either optical aniseikonia (from a difference in spectacle magnification between the eyes) or from induced prism when looking away from the optical center of the lenses (Prentice rule). To add to the potential confusion, contact lenses will treat both induced prism and optical aniseikonia. Differentiating between these two is to test for aniseikonia using the different methods discussed in the treatment section or to observe whether spectacle correction does not require looking away from the optical center (such as separate single vision distance and reading glasses) to alleviate the symptoms.

Altered brain function can cause micropsia and macropsia, and other distortions and can occur in conditions such as Alice in Wonderland syndrome, Charles Bonnet syndrome, migraine, and other types of hallucinations.[24][25] While these conditions may present with complaints that resemble those of aniseikonia, they can be ruled out as they generally affect both eyes and are present only temporarily.

Retinal pathology is often associated with symptoms of aniseikonia but has not caused retinal aniseikonia. Since retinal aniseikonia is generally treated medically and not optically, testing for aniseikonia is usually not done, and optical solutions are not pursued. Therefore, in many cases, it is not clear whether the blur caused by the retinal pathology is the cause of the symptoms instead of the presence of aniseikonia.

Prognosis

Optical aniseikonia generally has an excellent prognosis as most refractive conditions can be treated with surgery or contact lenses. If neither surgery nor contact lenses are an option, then aniseikonic spectacles are also available. 

Retinal aniseikonia has a good prognosis in most cases. In the case of retinal edema, central serous chorioretinopathy is generally a self-limited condition that reverses without treatment. Other causes of edema are generally treated successfully with medication or surgery. In the case of macula shrinking, such as can be caused by a staphyloma, there is no medical treatment. While macropsia can be treated with aniseikonic spectacles, the associated barrel distortion can not be treated.

Amblyopia: If aniseikonia has resulted in amblyopia and the patient is under nine years of age, then treatment for amblyopia according to the Pediatric Eye Disease Investigator Group guidelines will significantly improve visual outcomes. If aniseikonia has caused amblyopia and suppression of one eye and the patient is older than nine years, the prognosis is considerably worse.

Complications

Amblyopia. When aniseikonia is missed in children during the amblyogenic age (until age 8 to 10), it can result in permanent vision loss from amblyopia.

Ongoing symptoms of asthenopia, dizziness, diplopia, reduced ability to do visual tasks or headache. When aniseikonia is not detected or not treated adequately, the impact on the visual function can be tremendous.

Loss of binocular function. When aniseikonia cannot be treated, the patient may develop suppression, strabismus, or in the presence of persistent diplopia, may choose to occlude the eye. This results in a loss of binocularity and depth perception. 

Loss of the benefit of ophthalmic surgery: Ophthalmic surgery, such as scleral buckle procedures, monocular cataract extraction, or corneal transplant procedure, generally results in an excellent monocular visual outcome. When aniseikonia interferes with binocular function, patients may feel they are functionally worse off than before their surgery. 

Contact lens complications. Treatment with contact lenses increases the risk of contact lens-related dry eye, corneal infection and inflammation, allergies, and increased stress related to contact lens insertion and removal technique and complications.

Iseikonic lens complications. Iseikonic lenses can induce prism and distortion, and the use of the lenses is often not completely problem free. The lenses also affect the cosmetic appearance of the patient due to the magnification of one eye.

Deterrence and Patient Education

Deterrence Can Present in Several Forms

• Providing eye exams at an early age to detect anisometropia and aniseikonia and implement treatment to avoid amblyopia.
• Prompt referral for medical or surgical treatment for diseases that cause aniseikonia. Conditions that often cause aniseikonia include:
  • Cataracts: Timely referral for surgery can avoid a monocular refractive shift that causes anisometropia and aniseikonia.
  • Keratoconus: It often occurs in the second decade of life and can be treated effectively with contact lenses or surgery. Corneal crosslinking procedures can stop or slow down the progression but need to be initiated at an early stage.
  • Epiretinal membrane: Causes different distortion types of aniseikonia.
• Good planning of ocular surgeries to avoid creating aniseikonia. Common causes of iatrogenic aniseikonia include:
  • Monovision refractive or cataract surgery: In these cases, one eye is corrected for near use, the other for distance. If the patient can not adapt, spectacle correction may result in aniseikonia and is not tolerated.
  • Second-eye cataract surgery. The second eye is delayed to have cataract surgery in about 30% of patients with cataract surgery of the first eye. Careful planning on the refractive outcome is essential to avoid aniseikonia while the patient is waiting for the second-eye cataract to mature.
  • Scleral buckle and insertion of silicone oil procedures for retinal detachment: These procedures may generate enough anisometropia to produce symptoms of aniseikonia. There is evidence that retinal detachment surgery can often be done without using a scleral buckle.[58][59]

Patient Education

• Review and planning of surgical options. In some cases, a fitting with contact lenses can be done to simulate monovision correction to ensure the patient can tolerate the planned refractive change.
• Review and planning of optical options. These include correction with spectacles (full correction, one eye undercorrected, iseikonic lenses), contact lenses, and contact lens-spectacle combinations.
• Review of and planning of medical treatments. This can be the case in patients that have developed retinal aniseikonia but also in patients that require orthokeratology or myopia management in the case of developmental anisometropia.

Enhancing Healthcare Team Outcomes

Collaboration among ophthalmologists, neurologists, primary care doctors, optometrists, and opticians will allow for improved healthcare outcomes due to more prompt and accurate diagnosis, better treatment, and less risk of amblyopia, loss of binocularity, and loss of quality of life due to asthenopia, dizziness, diplopia, nervousness, headache, imbalance, nausea, spectacle intolerance, and distorted space perception. Neurologists and primary care doctors should include aniseikonia in their differential diagnosis when aniseikonia-specific symptoms are reported by a patient and refer to an ophthalmologist or optometrist for additional investigation.

When possible, ophthalmologists should avoid performing procedures likely to cause aniseikonia and promote procedures that can treat aniseikonia. Optometrists and ophthalmologists should treat aniseikonia with optical means such as contact lenses and contact lenses in combination with spectacles and refer for iseikonic spectacles when needed. Opticians should be trained on the optics and manufacture of iseikonic lenses and how to make them as cosmetically appealing and user-friendly as possible.